High prevalence of arterial thrombosis in JAK2 mutated essential thrombocythaemia: independence of the V617F allele burden

Abstract Heparin-induced thrombocytopenia is a serious complication of systemic heparin therapy. Patients with this disorder develop antibodies to the heparin-platelet factor 4 (H-PF4) complex. Patients with H-PF4 antibodies are at higher risk of venous and arterial thrombosis independently of the platelet count. Hemodialysis (HD) patients are repeatedly exposed to heparin to prevent thrombosis of the extra-corporeal circuit. However, thrombosis remains a frequent complication of vascular access, which accounts for up to 20% of all hospitalization in HD patients. Studies to date on H-PF4 antibody and vascular access thrombosis in HD patients have produced conflicting data but have been limited by small sample sizes. We sough to determine the prevalence of H-PF4 antibodies in a large cohort of HD patients and the correlation with vascular access thrombosis. Pre-dialysis blood samples were drawn on 419 HD patients; 107 cases with access thrombosis and 312 controls that never had access thrombosis. H-PF4 antibodies were measured twice using an ELISA (GTI PF4 Enhanced, GTI Diagnostics). The average of the two measurements was used in this analysis. All patients received unfractionated heparin while on dialysis. The mean age was 64 16 yrs with 62% male patients. Antibodies to H-PF4 were positive in 54 (12.9%) patients. H-PF4 antibodies were present in 10 (10.5%) of patients with confirmed access thrombosis and in 44 (15.1%) of controls. Hemodialysis with repeated exposure to systemic unfractionated heparin is associated with a high prevalence of H-PF4 antibodies. Although H-PF4 antibodies contribute to hypercoagulability leading to thrombotic complications, our results are not supporting a correlation between H-PF4 antibodies and vascular access thrombosis. Given the potential for venous and arterial thrombosis and the implications of our findings further investigations are needed in this population.

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Characteristics of Chinese patients with antiphospholipid syndrome and the ability of lupus anticoagulant assays to identify them

Clinical Chemistry and Laboratory Medicine (CCLM) ◽

10.1515/cclm-2016-0129 ◽

2016 ◽

Vol 54 (11) ◽

Author(s):

Ning Tang ◽

Ziyong Sun ◽

Shiyu Yin

Keyword(s):

Antiphospholipid Syndrome ◽

Lupus Erythematosus ◽

Arterial Thrombosis ◽

Lupus Anticoagulant ◽

Chinese Population ◽

Chinese Patients ◽

Clotting Time ◽

Systemic Lupus ◽

High Prevalence ◽

Positive Population

AbstractBackground:The objective of the work was to study the manifestations of antiphospholipid syndrome (APS) in the Chinese population, and evaluate the ability of lupus anticoagulant (LAC) assays to identify APS.Methods:Consecutive patients with APS from 2012 to 2015 in our hospital were recruited, strictly following the Sydney revised Sapporo criteria for APS classification. Meanwhile, in the LAC-positive population, LAC normalized ratios obtained from diluted Russell viper venom time (DRVVT) and silica clotting time (SCT) assays were compared between patients with and without APS.Results:One hundred and seventeen patients with defined APS comprised 86 women and 31 men with a mean age of 38 years (range 9–78 years), 38 (32.5%) of them had systemic lupus erythematosus. The prevalence of arterial thrombosis, venous thrombosis and obstetric complications were 46.2%, 25.6% and 30.8%, respectively. LAC was detected in 105 patients (89.7%), anti-βConclusions:A high prevalence of arterial thrombosis and LAC-positive result was noted in Chinese patients with APS, and an appropriate threshold for LAC normalized ratios could help to discriminate APS from non-APS patients in the LAC-positive population.

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The Study of Some Possible Risk Factors for Arterial Thrombosis in the Example of Georgian Patients

10.5772/intechopen.96121 ◽

2021 ◽

Author(s):

Marina Koridze ◽

Marina Nagervadze ◽

Maria Sarkhaiani ◽

Leila Akhvlediani ◽

Rusudan Khukhunaishvili ◽

...

Keyword(s):

Venous Thrombosis ◽

Blood Group ◽

Arterial Thrombosis ◽

Smoking Habit ◽

Control Group ◽

Similar Distribution ◽

High Prevalence ◽

Mn Blood Group ◽

Diet Type ◽

Healthy Persons

Cardiovascular diseases (CVD) are the most common cause of death worldwide. As arterial as venous thrombosis are major cause’s morbidity and mortality. There is an exponential increase in the risk of arterial and venous thrombotic events with age, gender, smoking habits, diet type etc. The association of arterial and venous thrombosis and ABO histo-blood group is well established. Our research aim was to find a possible relationship between age, gender, smoking habit, ABO, Rh, Kell, MN blood group and arterial thrombosis in the example of the Georgian population. The study material comprised the blood samples of 100 patients with arterial thrombosis. Also, control (donor) groups were studied. The Control group included individuals without cardiovascular disease during the 2019–2020 periods. They were asymptomatic, healthy persons. The immunoserological express method with universal monoclonal antibodies ware used. 77% of the studied patients were males. The majority of patients were over the 60 years old. 35% of our studied patients are non-smoker, 39% are ex-smoker, and 26% are active smokers. A similar distribution has the ABO and Rh phenotypes in patients and donors. M+ N+ (MN) the phenotype is relatively high in the patient group to comparing to donors. Kell antigen prevalence was relatively high in studied patients. Our study has shown maleness as a higher risk factor for arterial thrombosis. The smokers have a more predicted chance for arterial thrombosis. K+ phenotype and M+ N+ characteristics are a high prevalence in patients. There is no correlation between ABO and Rh blood groups with arterial thrombosis.

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Predictive Diagnostic and Prognostic Value of Platelets Microparticles (PMP), but Not of Reticulated Platelets (RP) or CD36 Expression in Essential Thrombocythaemia.

Blood ◽

10.1182/blood.v104.11.4745.4745 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4745-4745

Author(s):

Catherine Ternisien ◽

Marie-Pierre Moles ◽

Aline Tanguy-Schmidt ◽

Irene Dobo ◽

Martine Gardembas ◽

...

Keyword(s):

Venous Thrombosis ◽

Arterial Thrombosis ◽

Biological Marker ◽

Oral Chemotherapy ◽

Essential Thrombocythaemia ◽

Thrombotic Risk ◽

Diagnosis And Prognosis ◽

Reticulated Platelets ◽

Cd36 Expression ◽

Diagnostic And Prognostic Value

Abstract At the present time, Essential Thrombocythaemia (ET) remains an exclusion diagnostic since no diagnostic finding can definitely distinguish between clonal and reactive thrombocytosis (RT). In addition, no biological marker predicts readily the thrombotic risk of ET. We investigated by flowcytometry the diagnosis and prognosis value of PMP, RP and CD36 expression, as platelets parameters easily available in routine laboratory in 34 ET patients and 49 controls. Membrane platelet CD36 expression were stained by indirect immunofluorescence with specific anti-CD36 antibody and anti mouse IgG FITC (Biocytex, France), analyzed on FACSCalibur cytometer (BD), quantified using the calibration beads (Platelet Calibrator, Biocytex) and expressed as antigen molecules/platelet. RP were determined after RNA thiazole orange labeling (10 ng/ml, 45 min, at room temperature, in the dark). Assays performed after TRAP (Thrombin receptor activating peptide) stimulation demonstrated the specificity of the labeling (data not shown). PMP were identified on forward and side scatter after CD41a-PE or isotype control (Immunotech) labeling. ET was diagnosed according to revised PVSG criteria in 11 men and 23 women. The median age was 63 y (24–85) and the median platelet count was 674 x109/l (249–1324). At the time of evaluation, 19 patients received antiplatelets therapy, 9 oral chemotherapy, 10 exhibit arterial thrombosis (AT), 1 venous thrombosis and one, included in the AT group, experimented venous thrombosis as well. RP, CD36 and PMP were significantly increased in ET as compared to controls (P =.01, 10−4, <10−5, respectively). RP and CD36 expression were not significantly different between patients according to AT, antiplatelets agents and oral chemotherapy patterns. However PMP were significantly higher in patients with AT than in patients without thrombosis history (P =.02). We could not observe any decrease of PMP in patients with antiplatelets drugs since all patients with thrombosis had also antiplatelets therapy. In conclusion, RP, CD36 and PMP are increased in ET. These platelets parameters are currently evaluated in RT. The effects of antiplatelets agents on PMP and the thrombotic risk will have to be evaluated prospectively. N RP (platelet %) CD36 (Nb/platelet) PMP (Nb/platelet) control 49 3.86 (1.16–21.2) 9164 (4141–16254) 4632 (2073–13225) ET 34 5.78 (2.24–15.52) 10734 (5155–19920) 27928 (10905–117669) Arterial Thrombosis 10 6.73 (2.93–12.52) 9613 (5441–16096) 29948 (10905–117669) No thrombosis 23 5.78 (2.24–15.5) 11024 (5155–19920) 26173 (12377–72895) aspirin/clopidogrel 19 6.14 (2.93–13.75) 10543 (5155–16275) 32280 (10905–117669) no aspirin 15 5.78 (2.24–15.52) 10925 (8992–19929) 23586 (12377–72895) hydroxyurea 9 5.02 (2.24–13.84) 14478 (8560–19924) 37451 (17315–117669) no hydroxyurea 25 6.84 (2.91–15.52) 10012 (5155–16275) 26171 (12377–72895)

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Modulation of JAK2 V617F allele burden dynamics by hydroxycarbamide in polycythaemia vera and essential thrombocythaemia patients

British Journal of Haematology ◽

10.1111/j.1365-2141.2010.08467.x ◽

2011 ◽

Vol 152 (4) ◽

pp. 413-419 ◽

Cited By ~ 16

Author(s):

Carlos Besses ◽

Alberto Álvarez-Larrán ◽

Luz Martínez-Avilés ◽

Sergi Mojal ◽

Raquel Longarón ◽

...

Keyword(s):

Jak2 V617f ◽

Polycythaemia Vera ◽

Essential Thrombocythaemia ◽

Allele Burden

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Pruritus in Polycythemia Vera Is More Prevalent in Non-Smokers and Is Independently Associated with a Lower Risk of Arterial Thrombosis.

Blood ◽

10.1182/blood.v110.11.2550.2550 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2550-2550

Author(s):

Naseema Gangat ◽

Jacob J. Strand ◽

Terra L. Lasho ◽

Chin-Yang Li ◽

Animesh Pardanani ◽

...

Keyword(s):

Bone Marrow ◽

Polycythemia Vera ◽

Arterial Thrombosis ◽

Lower Risk ◽

World Health ◽

Study Cohort ◽

Clinical Correlates ◽

Allele Burden ◽

Jak2v617f Allele Burden

Abstract Background: Pruritus in polycythemia vera (PV) has been associated with a high JAK2V617F allele burden (Tefferi et al. Cancer. 2006;106:631, Vannucchi et al, Leukemia2007, in press). However, there is limited information regarding clinical correlates of pruritus per se in PV. Accordingly, we conducted a large (n=418) retrospective study in PV to accurately assess the prevalence and severity of pruritus as well as its relationship with presenting clinical features, bone marrow JAK2V617F allele burden, and prognosis. Methods: The study cohort consisted of a consecutive group of patients with PV who fulfilled the World Health Organization (WHO) diagnostic criteria and in whom information regarding the presence or absence of pruritus at diagnosis was fully documented. Pruritus was graded as being mild, moderate, or severe based on careful review of patient history. Results: Prevalence and severity of pruritus: A total of 418 patients fulfilled the above stipulated criteria for study inclusion (median age of 60 years; 56% males; median follow-up of 73 months). Of these, 131 (31%) experienced pruritus at time of initial diagnosis: mild in 97 patients (74%), moderate in 22 (17%), and severe in 12 (9%). Most patients with mild pruritus (n=92) received no specific therapy for pruritus whereas all 12 patients with severe pruritus required treatment; all 7 patients who received treatment with paroxetine responded. Pruritus and JAK2V617F allele burden: Quantitative measurement of JAK2V617F was performed in 64 patients using genomic DNA from archived bone marrow obtained at the time of PV diagnosis. Mutational frequency was 97%; median mutant allele burden was 25.4% (range 0.2 - 93.3%). Among the 62 V617F-positive patients, 24 (39%) had pruritus; the proportion of patients in the upper and lower quartile allele burden ranges were 50% and 0% in the presence of pruritus and 18% and 34% in its absence (p=0.002). Clinical correlates of pruritus: Pruritus was more prevalent in non-smokers (35% vs. 19%; p=0.004) and non-diabetics (33% vs. 16%; p=0.04) and was associated with a lower rate of arterial thrombosis at diagnosis (8% vs. 17%; p=0.01) as well as during follow-up (16% vs. 30%; p=0.003). These significant associations remained intact during multivariable analysis. Pruritus did not have an impact on the rate of leukemic or fibrotic transformation. Conclusions: Pruritus in PV is independently associated with a lower risk of arterial thrombosis despite high JAK2V617F allele burden and is also more prevalent in non-smokers. These observations suggest that pruritus might be a surrogate for an underlying platelet pathology with functional relevance.

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JAK2V617F mutation and allele burden are associated with distinct clinical and morphological subtypes in patients with essential thrombocythaemia

Journal of Clinical Pathology ◽

10.1136/jclinpath-2012-200804 ◽

2012 ◽

Vol 65 (10) ◽

pp. 953-955 ◽

Cited By ~ 8

Author(s):

Achille Pich ◽

Ludovica Riera ◽

Eloise Beggiato ◽

Barbara Nicolino ◽

Laura Godio ◽

...

Keyword(s):

Jak2v617f Mutation ◽

Essential Thrombocythaemia ◽

Allele Burden

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Bioelectronic Measurement of Nasality in Trainable Mentally Retarded Children

Journal of Speech and Hearing Disorders ◽

10.1044/jshd.4203.436 ◽

1977 ◽

Vol 42 (3) ◽

pp. 436-439 ◽

Cited By ~ 2

Author(s):

David A. Daly

Keyword(s):

Mentally Retarded ◽

High Prevalence ◽

Mentally Retarded Children ◽

Trainable Mentally Retarded

Fifty trainable mentally retarded children were evaluated with TONAR II, a bioelectronic instrument for detecting and quantitatively measuring voice parameters. Results indicated that one-half of the children tested were hypernasal. The strikingly high prevalence of excessive nasality was contrasted with results obtained from 64 nonretarded children and 50 educable retarded children tested with the same instrument. The study demonstrated the need of retarded persons for improved voice and resonance.

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